Coagulation factor 9-deficient mice are protected against dextran sulfate sodium-induced colitis

被引:4
作者
Khandagale, Avinash [1 ,2 ]
Kittner, Jens M. [3 ]
Mann, Amrit [1 ]
Ascher, Stefanie [1 ]
Kollar, Bettina [1 ]
Reinhardt, Christoph [1 ,4 ]
机构
[1] Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, CTH, Langenbeckstr 1, D-55131 Mainz, Germany
[2] Karolinska Inst, Inst Environm Med, SE-17177 Stockholm, Sweden
[3] Johannes Gutenberg Univ Mainz, Univ Med Ctr Mainz, Dept Med 1, Langenbeckstr 1, D-55131 Mainz, Germany
[4] German Ctr Cardiovasc Res DZHK, Partner Site RheinMain, Mainz, Germany
来源
BIOLOGY OPEN | 2018年 / 7卷 / 07期
关键词
Hemophilia B; Coagulation factor IX; Toll-like receptor-2; Colitis; Microbiota; INFLAMMATORY-BOWEL-DISEASE; TISSUE FACTOR; FACTOR-IX; BLOOD-COAGULATION; MOUSE MODEL; ACTIVATION; THROMBIN; EXPRESSION; GENERATION; RECEPTORS;
D O I
10.1242/bio.034140
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolism. Interestingly, IBD occurs less frequently in patients with inherited bleeding disorders. Therefore, we analyzed whether F9-deficiency is protective against the onset of acute colitis in a genetic hemophilia B mouse model. In the 3.5% dextran sulfate sodium (DSS)-induced colitis model, F9-deficient mice were protected from body-weight loss and had a reduced disease activity score. We detected decreased colonic myeloperoxidase activity and decreased CXCL1 levels in DSS-treated F9-deficient mice compared with wild-type (WT) littermate controls, indicating decreased neutrophil infiltration. Remarkably, we identified expression of coagulation factor IX (FIX) protein in small intestinal epithelial cells (MODE-K). In epithelial cell cultures, cellular FIX protein expression was increased following stimulation with the bacterial Toll-like receptor agonists lipopolysaccharide, macrophage-activating lipopeptide-2 and Pam3CSK4. Thus, we revealed a protective role of F9-deficiency in DSS-induced colitis and identified the intestinal epithelium as a site of ectopic FIX. This article has an associated First person interview with the first author of the paper.
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页数:5
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共 31 条
  • [1] Continuous Active State of Coagulation System in Patients With Nonthrombotic Inflammatory Bowel Disease
    Alkim, Huseyin
    Ayaz, Selime
    Alkim, Canan
    Ulker, Aysel
    Sahin, Burhan
    [J]. CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS, 2011, 17 (06) : 600 - 604
  • [2] Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis
    Anthoni, Christoph
    Russell, Janice
    Wood, Katherine C.
    Stokes, Karen Y.
    Vowinkel, Thorsten
    Kirchhofer, Daniel
    Granger, D. Neil
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (07) : 1595 - 1601
  • [3] Elevated sevum levels and reduced immunohistochemical expression of thrombomodulin in active ulcerative colitis
    Boehme, MWJ
    Autschbach, F
    Zuna, I
    Scherbaum, WA
    Stange, E
    Raeth, U
    Sieg, A
    Stremmel, W
    [J]. GASTROENTEROLOGY, 1997, 113 (01) : 107 - 117
  • [4] Coagulation factor Xa signaling: the link between coagulation and inflammatory bowel disease?
    Borensztajn, Keren
    Peppelenbosch, Maikel P.
    Spek, C. Arnold
    [J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 2009, 30 (01) : 8 - 16
  • [5] Inflammation and coagulation in inflammatory bowel disease: The clot thickens
    Danese, Silvio
    Papa, Alfredo
    Saibeni, Simone
    Repici, Alessandro
    Malesci, Alberto
    Vecchi, Maurizio
    [J]. AMERICAN JOURNAL OF GASTROENTEROLOGY, 2007, 102 (01) : 174 - 186
  • [6] Increased Procoagulant Function of Microparticles in Pediatric Inflammatory Bowel Disease: Role in Increased Thrombin Generation
    Deutschmann, Andrea
    Schlagenhauf, Axel
    Leschnik, Bettina
    Hoffmann, Karl Martin
    Hauer, Almuthe
    Muntean, Wolfgang
    [J]. JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2013, 56 (04) : 401 - 407
  • [7] ACTIVATION OF BLOOD-COAGULATION IN CROHNS-DISEASE - INCREASED PLASMA FIBRINOPEPTIDE A LEVELS AND ENHANCED GENERATION OF MONOCYTE TISSUE FACTOR ACTIVITY
    EDWARDS, RL
    LEVINE, JB
    GREEN, R
    DUFFY, M
    MATHEWS, E
    BRANDE, W
    RICKLES, FR
    [J]. GASTROENTEROLOGY, 1987, 92 (02) : 329 - 337
  • [8] Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases
    Frank, Daniel N.
    Amand, Allison L. St.
    Feldman, Robert A.
    Boedeker, Edgar C.
    Harpaz, Noam
    Pace, Norman R.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (34) : 13780 - 13785
  • [9] FACTOR-XI ACTIVATION IN A REVISED MODEL OF BLOOD-COAGULATION
    GAILANI, D
    BROZE, GJ
    [J]. SCIENCE, 1991, 253 (5022) : 909 - 912
  • [10] Enterobacteriaceae Act in Concert with the Gut Microbiota to Induce Spontaneous and Maternally Transmitted Colitis
    Garrett, Wendy S.
    Gallini, Carey A.
    Yatsunenko, Tanya
    Michaud, Monia
    DuBois, Andrea
    Delaney, Mary L.
    Punit, Shivesh
    Karlsson, Maria
    Bry, Lynn
    Glickman, Jonathan N.
    Gordon, Jeffrey I.
    Onderdonk, Andrew B.
    Glimcher, Laurie H.
    [J]. CELL HOST & MICROBE, 2010, 8 (03) : 292 - 300